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Journal article
Restricting mitochondrial GRK2 post-ischemia confers cardioprotection by reducing myocyte death and maintaining glucose oxidation
Science signaling, v 11(560)
11 Dec 2018
PMID: 30538174
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Increased abundance of GRK2 [G protein-coupled receptor (GPCR) kinase 2] is associated with poor cardiac function in heart failure patients. In animal models, GRK2 contributes to the pathogenesis of heart failure after ischemia-reperfusion (IR) injury. In addition to its role in down-regulating activated GPCRs, GRK2 also localizes to mitochondria both basally and post-IR injury, where it regulates cellular metabolism. We previously showed that phosphorylation of GRK2 at Ser(670) is essential for the translocation of GRK2 to the mitochondria of cardiomyocytes post-IR injury in vitro and that this localization promotes cell death. Here, we showed that mice with a S670A knock-in mutation in endogenous GRK2 showed reduced cardiomyocyte death and better cardiac function post-IR injury. Cultured GRK2-S670A knock-in cardiomyocytes subjected to IR in vitro showed enhanced glucose-mediated mitochondrial respiratory function that was partially due to maintenance of pyruvate dehydrogenase activity and improved glucose oxidation. Thus, we propose that mitochondrial GRK2 plays a detrimental role in cardiac glucose oxidation post-injury.
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Details
- Title
- Restricting mitochondrial GRK2 post-ischemia confers cardioprotection by reducing myocyte death and maintaining glucose oxidation
- Creators
- Priscila Y. Sato - Drexel UniversityJ. Kurt Chuprun - Temple UniversityLaurel A. Grisanti - University of MissouriMeryl C. Woodall - Temple UniversityBrett R. Brown - Temple UniversityRajika Roy - Temple UniversityChristopher J. Traynham - Temple UniversityJessica Ibetti - Temple UniversityAnna M. Lucchese - Temple UniversityAncai Yuan - Temple UniversityKonstantinos Drosatos - Temple UniversityDoug G. Tilley - Temple UniversityErhe Gao - Temple UniversityWalter J. Koch - Temple University
- Publication Details
- Science signaling, v 11(560)
- Publisher
- Amer Assoc Advancement Science
- Number of pages
- 9
- Grant note
- W.W. Smith Charitable Trust R37HL061690 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) R37 HL061690; P01 HL075443; P01 HL091799; HL130218 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA American Heart Association
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000452741700004
- Scopus ID
- 2-s2.0-85058292749
- Other Identifier
- 991019167913104721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology